Imidafenacin

Imidafenacin tablets are the first-line drug for the treatment of overactive bladder (OAB). However, the tablets need to be taken twice daily for up to 3-6 months, which highly reduces patient compliance. This study aimed to develop a long-acting imidafenacin transdermal patch (LAITP) with high drug loading using amorphous solid dispersion technology (ASD). ASD, consisting of polyvinyl pyrrolidone and imidafenacin, not only significantly increased the drug loading in the patch, but also inhibited drug crystallization. Furthermore, the formation mechanism of ASD was systematically elucidated using SEM, XRD, DSC, FT-IR, and molecular docking. The LAITP was optimized through single-factor investigations and ternary phase diagram analysis. It was confirmed by SEM and confocal Raman microscopy that ASD was a spherical microparticle with a size of 28.62 ± 8.91 µm in LAITP. Notably, under long-term and accelerated conditions of 3 months, the LAITP exhibited excellent stability to ensure the reliability of quality. Importantly, human pharmacokinetic studies demonstrated that LAITP with low skin irritation and favorable adhesion properties prolonged sustained effective plasma concentration in comparison to commercial tablets (Staybla®), reducing the frequency of administration and thereby improving patient compliance, which is expected to be a promising treatment option for patients with OAB.

The gut microbiota can act as a buffer against changes in energy and food availability and adapt plastically to fluctuations in the host's diet. However, it is unknown how changes in the gut microbiome with the seasons impact microbial metabolism and the accessibility of nutrients to hosts. The study utilized 16S rRNA and UHPLC-MS/MS approaches to examine seasonal fecal metabolome variations in the captive Yangtze finless porpoises (YFPs) to determine if these variations are linked to nutrient intake or gut microbiome composition changes. The YFPs were mostly fed a frozen and live fish diet, with different food intakes yearly. We found that gut microbial diversity remained constant, but community structure varied seasonally. Firmicutes and Cyanobacteria were higher in winter, Actinobacteria in spring and fall, and proteobacteria in summer. The genus Paeniclostridium was significantly higher in the spring season, Romboutsia and Clostridium_sensu_stricto_13 were significantly higher in the summer, while Terrisporobacter and Macrococcus were significantly higher in the fall group. The study reported that seasonal dietary variation significantly impacted the fecal metabolome by affecting the metabolism, including energy, amino acid, carbohydrate, and nucleotide metabolism of the captive YFP. Moreover, significant correlations between metabolome and microbiome were found, and these correlations may indicate that the captive YFP has adapted to cope with dietary variations and enhance energy acquisition. These findings improve our knowledge of the link between microbiota, diet, metabolites, and the physiology of the host and suggest that gut microbial populations may adapt continuously to changes in diet.